FDA Approves Revtorpyk (gedatolisib) for the Treatment of HR+/HER2-, PIK3CA Wild-Type Locally Advanced or Metastatic Breast Cancer

Celcuity Inc. (Nasdaq: CELC), a biotechnology company focused on developing and commercializing targeted therapies for multiple solid tumor indications,   announced  the U.S. Food and Drug Administration (“FDA”) approval of  Revtorpyk (gedatolisib) for the treatment of patients with hormone receptor positive (“HR+”), human epidermal growth factor receptor 2 negative (“HER2-”), locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Revtorpyk is the only inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2 to receive FDA approval.

• Revtorpyk is the first and only FDA-approved therapy that inhibits all class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2
• In the Phase 3 VIKTORIA-1 trial, Revtorpyk combined with palbociclib and fulvestrant and Revtorpyk combined with fulvestrant reduced the risk of disease progression or death by 76% and 67%, respectively, compared to fulvestrant among patients with PIK3CA wild-type advanced or metastatic breast cancer

“The PI3K/AKT/mTOR, or PAM, pathway is one of the most important targets in cancer, but comprehensively inhibiting it has stymied researchers and drug developers for nearly two decades,” said Brian Sullivan, CEO and co-founder of Celcuity. “Revtorpyk addressed this 20-year challenge by becoming the first pan-PI3K, mTORC1/2 inhibitor approved by the FDA. We are thankful for the opportunity to make this important new therapy available to patients with HR+/HER2- locally advanced or metastatic breast cancer.”

HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers.1 Among this breast cancer subtype, approximately 60% have PIK3CA wild-type disease.2

“For patients with HR+/HER2- locally advanced or metastatic breast cancer, there is an urgent need for new treatment options that can meaningfully increase the likelihood of survival without disease progression or death,” said Sara Hurvitz, MD, Senior Vice President, Clinical Research Division, Fred Hutchinson Cancer Center, Smith Family Endowed Chair in Women’s Health and Professor and Head, Division of Hematology and Oncology, University of Washington, School of Medicine and co-principal investigator for the VIKTORIA-1 trial. “With the approval of Revtorpyk, oncologists now have an effective new treatment option for these patients.”

The approval of Revtorpyk is based on positive clinical results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial, an open-label, global, randomized clinical trial evaluating the efficacy and safety of Revtorpyk plus fulvestrant, with or without palbociclib, for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 therapy and an aromatase inhibitor. In the VIKTORIA-1 trial, median progression free survival (“PFS”) with the Revtorpyk triplet (Revtorpyk plus palbociclib and fulvestrant) was 9.3 months versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months (HR=0.24; 95% CI: 0.17-0.35; p<0.0001). The objective response rate (“ORR”) of the Revtorpyk triplet was 32% compared to 1% with fulvestrant and the median duration of response (“DOR”) was 17.5 months. For the Revtorpyk doublet (Revtorpyk plus fulvestrant), the median PFS was 7.4 months versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months (HR=0.33; 95% CI: 0.24-0.48; p<0.0001). The ORR of the Revtorpyk doublet was 28% and the median DOR was 12.0 months. The median DOR was not determinable for fulvestrant because there was only one objective response.

“Today’s approval of Revtorpyk addresses a significant unmet need for the thousands of patients affected each year by HR+/HER2-, PIK3CA wild-type locally advanced or metastatic breast cancer whose disease has progressed after endocrine therapy,” said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. “We are deeply grateful to the patients and their caregivers, investigators and clinical study teams, and Celcuity team members who made this advancement possible.”

Celcuity anticipates commercial launch in late Q3 2026. Based on the company’s commitment to ensuring broad, affordable, and unrestricted patient access to Revtorpyk, we have designed a comprehensive patient support program. To make Revtorpyk available to patients prior to commercial launch, those who are eligible will be able to enroll in Celcuity’s expanded access program.

Celcuity plans to submit in Q3 2026 a supplemental New Drug Application (“sNDA”) to the FDA for Revtorpyk for the treatment of HR+/HER2-, PIK3CA mutated, locally advanced or metastatic breast cancer, following at least one line of endocrine therapy based on results from the mutant cohort of the Phase 3 VIKTORIA-1 trial. Results for this study were recently presented in a late-breaking abstract oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Following the sNDA submission, Celcuity intends to submit VIKTORIA-1 data for marketing authorization of gedatolisib to other regulatory authorities around the world.

Revtorpyk is also being studied in the ongoing Phase 3 VIKTORIA-2 clinical trial incorporating two independent studies evaluating two separate patient cohorts with HR+/HER2- locally advanced or metastatic breast cancer who are treatment-naive in the advanced setting.

About Revtorpyk (gedatolisib)

Revtorpyk is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT.3.4.5

Revtorpyk is in development for the first-line treatment of HR+/HER2- locally advanced or metastatic breast cancer and for the second-line treatment of metastatic castration resistant prostate cancer.

Indication Statement

Revtorpyk (gedatolisib) is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.

https://en.wikipedia.org/wiki/Gedatolisib

FDA Approves Revtorpyk (gedatolisib) for the Treatment of HR+/HER2-, PIK3CA Wild-Type Locally Advanced or Metastatic Breast Cancer

Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer

Arvinas, Inc. (Nasdaq: ARVN), today with its partner Pfizer Inc. (NYSE: PFE), announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for vepdegestrant for the treatment of patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ESR1-mutated advanced or metastatic breast cancer who have previously received endocrine-based therapy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 5, 2026.

“Patients often face limited treatment options after first-line treatment and vepdegestrant demonstrated improved progression-free survival in patients with ESR1-mutated ER+/HER2- advanced breast cancer,” said John Houston, Ph.D., Chairperson, Chief Executive Officer, and President at Arvinas. “With the efficacy and favorable tolerability seen in VERITAC-2, we believe vepdegestrant, if approved, has potential to be a best-in-class treatment option for patients in the second-line ESR1-mutant setting. We look forward to working alongside Pfizer and with the FDA to pursue vepdegestrant’s approval and to ensure this important treatment option is made available to patients as rapidly as possible.”

Vepdegestrant, an investigational oral PROTAC ER degrader, is being jointly developed by Arvinas and Pfizer. The NDA submission was based on data from VERITAC-2 (NCT05654623), a global, randomized Phase 3 clinical trial evaluating vepdegestrant versus fulvestrant. These data were recently presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting and were simultaneously published in The New England Journal of Medicine.

About Vepdegestrant

Vepdegestrant is an investigational, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) estrogen receptor degrader. Vepdegestrant is being developed as a potential monotherapy for ER+/HER2- advanced or metastatic breast cancer with estrogen receptor 1 (ESR1) mutations in the second line-plus setting.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for vepdegestrant for its use as a monotherapy in the treatment of adults with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-), ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy. Vepdegestrant has also been granted Fast Track designation by the FDA, underscoring the significant unmet need in this patient population and the potential for vepdegestrant to offer a meaningful new treatment option.

About the VERITAC-2 Clinical Trial

The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global, randomized trial evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor plus endocrine therapy. The trial enrolled 624 patients, 270 of whom had ESR1m positive disease, at 213 sites in 25 countries.

Patients were randomized 1:1 to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. In the trial, 43% of patients (n=270) had ESR1 mutations detected. The primary endpoint was progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations as determined by blinded independent central review. Overall survival is the key secondary endpoint.

https://en.wikipedia.org/wiki/Vepdegestrant

Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

Eli Lilly and Company (NYSE: LLY) announced  the U.S. Food and Drug Administration (FDA)  approval of  Inluriyo (imlunestrant, 200 mg tablets), an oral estrogen receptor antagonist, for the treatment of adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–), ESR1-mutated advanced or metastatic breast cancer (MBC) whose disease progressed after at least one line of endocrine therapy (ET). In the Phase 3 EMBER-3 trial, Inluriyo reduced the risk of progression or death by 38% versus ET. Among patients with ESR1-mutated MBC, Inluriyo significantly improved progression-free survival (PFS) versus fulvestrant or exemestane, with a median PFS of 5.5 months vs 3.8 months (HR=0.62 [95% CI: 0.46-0.82]); p-value=0.0008.

Inluriyo is a treatment for ER+, HER2–, ESR1-mutated MBC. Some breast cancers develop ESR1 mutations that can cause estrogen receptors to become overactive and drive cancer growth. Inluriyo binds, blocks, and facilitates the degradation of these receptors, helping to slow disease progression. Its once-daily dosing provides patients with an oral treatment option.

"This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "We are deeply grateful to the patients, investigators, Lilly team members and clinical care teams who made this advancement possible. This therapy has the potential to make the treatment journey more manageable for those living with breast cancer."

The Inluriyo label contains a warning and precaution for embryo-fetal toxicity.

The FDA approval is based on the results of the EMBER-3 trial in the patient population harboring ESR1-mutated MBC (n=256). Patients received Inluriyo or ET as first-line treatment for MBC following recurrence on adjuvant aromatase inhibitor (AI), +/- prior CDK4/6 inhibitor (21%), or as second-line treatment for MBC following progression on AI, +/- prior CDK4/6 inhibitor (79%).

"This represents an important advancement for patients with ESR1-mutated MBC, a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance," said Komal Jhaveri, M.D., FACP, FASCO, section head of Endocrine Therapy Research and clinical director of Early Drug Development at Memorial Sloan Kettering Cancer Center, and a principal investigator of EMBER-3. "With its demonstrated efficacy, tolerability profile and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."

In EMBER-3, the majority of adverse events (AEs) with Inluriyo were low grade (Grade 1-2) and the most common adverse reactions (≥10%), including laboratory abnormalities, were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain. In the study, 4.6% of patients permanently discontinued treatment due to AEs. Dose reductions and dose interruptions occurred in 2.4% and 10% of patients, respectively.

"The approval of Inluriyo expands the metastatic breast cancer treatment landscape for patients who test positive for the ESR1 mutation," said Jean Sachs, CEO, Living Beyond Breast Cancer. "Eligible patients will now have access to an additional treatment option, offering them the potential for flexibility in their daily lives and disease management, and—above all—renewed hope for the future."

Inluriyo is also being studied in the ongoing Phase 3 EMBER-4 trial in the adjuvant setting for people with ER+, HER2– early breast cancer (EBC) at increased risk of recurrence, which is enrolling approximately 8,000 patients worldwide.

https://en.wikipedia.org/wiki/Imlunestrant#:~:text=Society%20and%20culture-,Legal%20status,under%20the%20brand%20name%20Inluriyo.

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

FDA Approves Truqap (capivasertib) plus Faslodex for Patients with Advanced HR-Positive Breast Cancer

AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the US for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN). Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

The approval by the Food and Drug Administration (FDA) was based on the results from the CAPItello-291 Phase III trial published earlier this year in The New England Journal of Medicine.1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).

Breast cancer is the most common cancer and one of the leading causes of cancer-related death worldwide.2 HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.4-6 Endocrine therapies are widely used in this setting, but many patients develop resistance to 1st-line cyclin-dependent kinase (CDK) 4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional endocrine therapy-based options

Ref; https://en.wikipedia.org/wiki/Capivasertib

FDA Approves Truqap (capivasertib) plus Faslodex for Patients with Advanced HR-Positive Breast Cancer

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer

The Menarini Group (“Menarini”), a leading Italian pharmaceutical and diagnostics company, announced  the U.S. Food and Drug Administration (FDA)   approval of  Orserdu for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, headquartered in New York and focused on bringing transformational oncology treatments for cancer patients, will commercialize Orserdu in the U.S.

“The FDA approval of Orserdu marks the first ever therapy for ER+, HER2- advanced or metastatic breast cancer patients with ESR1 mutations and we are very proud to offer a targeted therapy addressing this huge unmet need,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. “We are grateful to the patients, investigators and administrators who participated in the clinical trials that led to this remarkable innovation.”

Orserdu is approved under the FDA’s Priority Review and Fast Track designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor ESR1 mutations.

In the group of patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. A post-hoc analysis of the PFS results based on the duration of prior CDK4/6i inhibitors (CDK4/6i) usage was presented at San Antonio Breast Cancer Symposium (SABCS) in December 2022. The median PFS was 8.6 months on elacestrant vs 1.9 months for SOC, in those patients whose tumors harbored ESR1 mutations and had been treated with a CDK4/6i for at least 12 months.

Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

“Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed,” said Dr. Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. “ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose.”

“Each year 300,000 Americans are diagnosed with breast cancer and metastatic breast cancer causes the vast majority of deaths from the disease: more than 43,000 annually. We urgently need new and better treatment options to extend and improve the lives of people with metastatic breast cancer,” said Sonya Negley, Executive Director, Metavivor. “We are thrilled to see the approval of Orserdu, a new oral endocrine therapy, for patients who have tumors that harbor ESR1 mutations, which are present in up to 40% of ER+, HER2- advanced or metastatic breast cancer. We advise patients to get tested for ESR1 mutations at progression in their metastatic treatment, so that their healthcare team can identify the right treatment options for their disease.“

Read More ...

https://en.wikipedia.org/wiki/Elacestrant

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer

Team finds that their cancer-fighting compound fights obesity and diabetes, too

Eric Prossnitz, Ph.D., and his team hope to help 93 million obese Americans fight their fat.

In a paper published in Science Translational Medicine, they reported that G-1, a cancer-fighting compound they discovered some years ago, reduces fat in obese mice. Although G-1 is currently in phase 1 clinical trials for cancer, Prossnitz and his team are planning preclinical studies to use G-1 to fight fat in obese people.

Obesity affects 40% of adults in the United States, resulting in health conditions that include heart disease, high blood pressure, type 2 diabetes and some cancers. According to the U.S. Centers for Disease Control and Prevention, obesity and its related conditions far outweigh other causes of death. Current drugs for obesity don't effectively reduce it or have undesirable side effects.

Prossnitz and his team have been studying GPER, the G protein-coupled estrogen receptor that G-1 activates, because GPER affects certain breast cancer cells. When breast cancer drugs like tamoxifen and fulvestrant block estrogen receptors in a cell's nucleus, they also activate GPER, which is found in cell membranes.

Prossnitz's previous studies showed that GPER may play a role in resistance to tamoxifen and similar drugs, and that led him to wonder how G-1 affects non-cancerous cells when estrogen is lacking.

Estrogen is considered a female hormone, although men produce it at low levels. Low estrogen in women is a hallmark of menopause, and postmenopausal women also have higher rates of heart disease, high blood pressure, obesity and diabetes. So to understand whether G-1 might affect metabolism in postmenopausal women, Prossnitz and his team studied mice with low estrogen levels.

In their studies, low-estrogen female mice gained weight rapidly, even on a normal diet, and quickly became obese and diabetic. When the researchers treated these obese female mice with G-1, the mice lost weight and their diabetes went away.

The researchers determined that the weight loss wasn't due to the mice eating less or moving around more; it resulted from what their bodies did with the calories they ate. Instead of storing calories as fat, the mice used them as fuel.

"Their metabolism changed," Prossnitz says. "The mice showed an increased energy expenditure."

Prossnitz's team also studied male mice, which have naturally low levels of estrogen. The male mice were fed a high-fat diet, which made them obese and diabetic, and then some were treated with G-1. Although the treated mice did not lose weight, they did not gain additional weight either, like the untreated mice. More importantly, their diabetes improved.

"This result suggests that G-1 has separate effects on obesity and diabetes," Prossnitz says. "The G-1-treated male mice were metabolically healthier, even though they were still obese."

Finally, the team also fed a high-fat diet to low-estrogen female mice. These mice became obese very quickly, but just like their sisters on a normal mouse diet, they lost weight and their diabetes improved when they were treated with G-1. These results, says Prossnitz, could point to a sex difference in the effects of the drug or in the way GPER signals in the cells of males and females.

To learn about how G-1 increases energy expenditure, the team studied brown fat cells, which generate heat instead of storing excess calories as fat. What they found surprised them: when treated with G-1, the cells expended more energy.

"This fits nicely with what we saw in mice," Prossnitz says, "and suggests that G-1 may reduce obesity by targeting brown fat cells that burn extra calories."

In a future series of experiments, Prossnitz plans to study how signals from GPER induce the cellular changes that cause more energy to be used. He hopes that one day soon G-1 could revolutionize the treatment of metabolic disorders.

In the meantime, he and his team are starting the long path toward clinical trials that will test the ability G-1 to fight obesity and diabetes in people.

https://stm.sciencemag.org/content/12/528/eaau5956/tab-figures-data

FDA Approves Piqray (alpelisib) as First PI3K Inhibitor for Breast Cancer

U.S. Food and Drug Administration approved Piqray (alpelisib) tablets, to be used in combination with the FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen.

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real-Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks.”

Metastatic breast cancer is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain). When breast cancer is hormone-receptor positive, patients may be treated with anti-hormonal treatment (also called endocrine therapy), alone or in combination with other medicines, or chemotherapy.

The efficacy of Piqray was studied in the SOLAR-1 trial, a randomized trial of 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed while on or after receiving an aromatase inhibitor. Results from the trial showed the addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.

Common side effects of Piqray are high blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), and hair loss.

Health care professionals are advised to monitor patients taking Piqray for severe hypersensitivity reactions (intolerance). Patients are warned of potentially severe skin reactions (rashes that may result in peeling and blistering of skin or mucous membranes like the lips and gums). Health care professionals are advised not to initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson Syndrome, erythema multiforme, or toxic epidermal necrolysis. Patients on Piqray have reported severe hyperglycemia (high blood sugar), and the safety of Piqray in patients with Type 1 or uncontrolled Type 2 diabetes has not been established. Before initiating treatment with Piqray, health care professionals are advised to check fasting glucose and HbA1c, and to optimize glycemic control. Patients should be monitored for pneumonitis/interstitial lung disease (inflammation of lung tissue) and diarrhea during treatment. Piqray must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

Piqray is the first new drug application (NDA) for a new molecular entity approved under the Real-Time Oncology Review (RTOR) pilot program, which permits the FDA to begin analyzing key efficacy and safety datasets prior to the official submission of an application, allowing the review team to begin their review and communicate with the applicant earlier. Piqray also used the updated Assessment Aid (AAid), a multidisciplinary review template intended to focus the FDA’s written review on critical thinking and consistency and reduce time spent on administrative tasks. 

https://en.wikipedia.org/wiki/Alpelisib

https://pubchem.ncbi.nlm.nih.gov/compound/Alpelisib

FDA Approves Ibrance (palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer

In continuation of my update on palbociclib

Pfizer  announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for Ibrance (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of Ibrance in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.

“With this approval, we are now able to offer Ibrance to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We appreciate that our partnership with the FDA has allowed us to take a significant step forward in the use of real-world data to bring medicines to patients who are most in need.”

Ibrance is now approved for adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy. With today’s approval, Ibrance is the first and only CDK 4/6 inhibitor indicated in combination with an aromatase inhibitor for the first-line treatment of men with HR+, HER2- metastatic breast cancer in the U.S.

“Men with breast cancer have limited treatment options, making access to medicines such as Ibrance critically important,” said Bret Miller, founder of the Male Breast Cancer Coalition. “We applaud the use of real-world data, a new approach to drug review, to make Ibrance available to certain men with metastatic breast cancer and help address an unmet need for these patients.”

Real-world data is playing an increasingly important role in expanding the use of already approved innovative medicines.1 Due to the rarity of breast cancer in males, fewer clinical trials are conducted that include men resulting in fewer approved treatment options. In the U.S. in 2019, it is estimated that there will be 2,670 new cases of invasive breast cancer and about 500 deaths from metastatic breast cancer in males.2 The 21st Century Cures Act, enacted in 2016, was created to help accelerate medical product development, allowing new innovations and advances to become available to patients who need them faster and more efficiently.3 This law places additional focus on the use of real-world data to support regulatory decision-making.4

Detailed analysis of the use of Ibrance in men with HR+, HER2- advanced or metastatic breast cancer will be presented at an upcoming medical meeting. Based on limited data from postmarketing reports and electronic health records, the safety profile for men treated with Ibrance is consistent with the safety profile in women treated with Ibrance.5

About Ibrance (palbociclib) 125 mg capsules

Ibrance is an oral inhibitor of CDKs 4 and 6,6 which are key regulators of the cell cycle that trigger cellular progression.7,8 In the U.S., Ibrance is indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

Ibrance currently is approved in more than 90 countries and has been prescribed to more than 200,000 patients globally.

Dual-Drug Therapy May Boost Odds Against a Tough Breast Cancer

In continuation of my updates on  fulvestrant (Faslodex) and anastrozole (Arimidex)

           

 There's good news for women battling a particularly difficult form of advanced breast cancer.

In a new study of patients with so-called "hormone receptor-positive" breast cancer that's spread beyond the breast, women who received a combo of two anti-estrogen drugs right away lived many months more than those who got just one drug, the researchers found.

The drugs -- fulvestrant (Faslodex) and anastrozole (Arimidex) -- appear to work better when given together rather than using fulvestrant as a follow-up drug given after anastrozole, according to the team led by Dr. Rita Mehta. She's a clinical professor at the University of California, Irvine.

"These results are very exciting," said Mehta, who is also a member of the Southwest Oncology Group breast cancer research committee.

"Women who are treated with fulvestrant up front live about eight months longer. That's a lot of extra time to do the things you love with the people you love," she said in an Oregon Health & Science University news release.

"Women who received fulvestrant, right up front, lived longer based on this new long-term analysis. This is credible evidence that combination endocrine therapy should be considered an option for first-line treatment of advanced hormone receptor-positive breast cancer," Mehta said.

One breast cancer specialist who wasn't involved in the research agreed.

"Although metastatic breast cancer is not thought to be curable, it can be controlled for years and converted to a chronic disease that allows patients to carry on with their lives," explained Dr. Alice Police. She directs breast surgery at Northwell Health Cancer Institute in Sleepy Hollow, N.Y.

That's true for all advanced breast cancers, including the hormone receptor-positive tumors covered by this study. About two-thirds of all breast cancers are of this type, according to the American Cancer Society.

These hormone-sensitive tumors "love estrogen," Police noted, and so oncologists typically prescribe anti-estrogen drugs to help slow the disease.

"Typically, a patient is treated sequentially with different medications [such as fulvestrant and anastrozole], and switched to a different medication if their cancer spreads or grows," she explained.

But what if women got the two drugs in combination, right away?

To answer that question, Mehta's group tracked outcomes for over 700 postmenopausal women with breast cancer treated at 73 hospitals, clinics and cancer centers across the United States and Canada.

The investigators found that women who received both medicines as their first line of treatment lived an average of eight months longer than those who took anastrozole alone -- 50 months versus 42 months.

The study findings also showed that 42 percent of women who got the combo treatment were alive five years after their treatment, compared with 33 percent of women who got anastrozole alone.

About 45 percent of women treated with anastrozole alone were later treated with fulvestrant, when their cancer got worse or spread. But those who initially received fulvestrant had the best overall survival and progression-free survival, the researchers reported March 27 in the New England Journal of Medicine.

The study also found that patients in the combo-treatment group received lower-than-normal doses of fulvestrant in the trial: 250 milligrams (mg) per month after the first loading dose, compared with the typical 500 mg per month.

The two drugs work in slightly different ways. Anastrozole reduces the body's production of estrogen, while fulvestrant disables the tumor's ability to "feed" on circulating estrogen.

https://en.wikipedia.org/wiki/Fulvestrant

https://en.wikipedia.org/wiki/Anastrozole

Dual-Drug Therapy May Boost Odds Against a Tough Breast Cancer 

Kisqali (ribociclib) Approved for Additional Indications in HR+/HER2- Advanced Breast Cancer

In continuation of my update on ribociclib

Novartis  announced a new approval for Kisqali (ribociclib) from the US Food and Drug Administration (FDA) for women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. Kisqali is now the only CDK4/6 inhibitor indicated for use with an aromatase inhibitor for the treatment of pre-, peri- or postmenopausal women in the US, and also is indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women[1]. FDA reviewed this supplemental New Drug Application (sNDA) under its Real-Time Oncology Review and Assessment Aid pilot programs and approved the application in less than one month after submission.

"Compelling data for Kisqali have led to the broadest first-line indications of any CDK4/6 inhibitor," said Liz Barrett, CEO, Novartis Oncology. "With this new approval Kisqali has the potential to help even more people in the US live a longer life without progression of disease from this incurable form of breast cancer."

This approval is based on the pivotal MONALEESA-7 and MONALEESA-3 Phase III clinical trials that demonstrated prolonged progression-free survival (PFS) and improvements as early as eight weeks for Kisqali-based regimens compared to endocrine therapy alone[1]. In MONALEESA-7, Kisqali plus an aromatase inhibitor and goserelin nearly doubled the median PFS compared to an aromatase inhibitor and goserelin alone (27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743) in pre- or perimenopausal women[1]. In MONALEESA-3, Kisqali plus fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732) across the overall population of first-line and second-line postmenopausal women[1].

"These MONALEESA clinical trial program data add to the body of evidence that CDK 4/6 inhibition, in the case of these studies with ribociclib, gives women diagnosed with HR+/HER2- advanced breast cancer an important first-line treatment option," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. "Based on Phase III trial results that consistently showed clinical benefit, physicians should be encouraged to re-evaluate treatment for advanced breast cancer in the first-line setting."

Approximately 155,000 people in the US are living with metastatic breast cancer[2]. Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure[3]. Advanced breast cancer in premenopausal women is a biologically distinct and more aggressive disease, and it is the leading cause of cancer death in women 20-59 years old[4],[5].

"Premenopausal women diagnosed with advanced breast cancer often face unique social challenges and a poorer prognosis. For the first time in nearly 20 years, we have results from a dedicated clinical trial among these women," said Jennifer Merschdorf, CEO, Young Survival Coalition. "With this approval, some younger women now have a new therapy indicated specifically for them that may help extend their lives without progression of disease."

Experimental Drug, Taselisib, Shows 'Modest' Benefit in Slowing Advanced Breast Cancer

A new and highly targeted drug slowed the growth of advanced breast cancers by about an average of two months, researchers report.

"The findings in this study show a modest benefit to a subgroup of women with estrogen receptor-positive tumors," said Dr. Stephanie Bernik, a breast cancer specialist who wasn't involved in the research.

Estrogen receptor-positive tumors are a common subtype of breast cancer that grow in the presence of estrogen. The experimental drug used in the new study, called taselisib, targets a gene called PIK3CA that's tied to cancer growth.

"About 40 percent of all patients with advanced breast cancer estrogen receptor-positive have PIK3CA mutations, which means they could benefit from taselisib," explained study author Dr. Jose Baselga. He's physician-in-chief at Memorial Sloan Kettering Cancer Center in New York City.

"Our findings are proof that targeting this pathway in breast cancer is effective. However, the benefit to patients was more modest than we had hoped for, and there is a risk of considerable side effects with the addition of taselisib," Baselga said in a news release from the American Society of Clinical Oncology (ASCO).

As the researchers explained, taselisib has already proven beneficial for people fighting head-and-neck cancers or certain gynecological tumors. Would it do the same for hormone-sensitive breast cancers?

To find out, Baselga's group worked with 516 women with either locally advanced or metastatic estrogen receptor-positive breast cancers. About two-thirds of the women received taselisib and a standard chemotherapy drug, fulvestrant, while the remaining third received fulvestrant and a placebo.

Women on the drug combo regimen had 30 percent lower odds of their cancer worsening, compared with those who got standard chemo alone, the study found. Women who got taselisib typically went an average of 7.4 months without signs that their cancer was worsening, compared to 5.4 months without the drug -- a two-month difference.

Tumor shrinkage was much more evident in women taking taselisib (28 percent of patients) versus those on fulvestrant alone (12 percent), the findings showed.

However, there was a downside: While 17 percent of women taking taselisib had to quit their treatment because of side effects, that was true for just 2 percent of those who weren't taking the medicine, the investigators found.

Still, Bernik said the study offers breast cancer patients some hope.

"Although tumor growth was only suppressed by two months, this medication opens the door to further investigation with drugs that target cancers with the PIK3CA gene mutation," she said.

"One would hope that because we know targeting this gene decreases tumor growth, perhaps combining it with various other drugs might make it more effective, and also direct research to developing other drugs that work in a similar fashion," Bernik reasoned.

Dr. Alice Police directs breast surgery at Northwell Health Cancer Institute in Sleepy Hollow, N.Y. She called targeted therapies like taselisib "a wonderful new field that looks for medications that keep cancer cells from growing while protecting normal tissue."

Still, "this drug was a little disappointing to the researchers in that its benefit was not as great as they had hoped, and the drug was more toxic than they had hoped," Police said.

The findings were scheduled for presentation on Saturday at ASCO's annual meeting, in Chicago. Because the new study was presented at a medical meeting, its findings should be considered preliminary until published in a peer-reviewed journal.

Lilly Receives Additional FDA Approval for Verzenio (abemaciclib), as Initial Treatment for Advanced Breast Cancer

In continuation of my update on Abemaciclib

Eli Lilly and Company  announced the U.S. Food and Drug Administration (FDA) has approval of  Verzenio (abemaciclib) in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. This additional FDA approval marks the third indication for Verzenio within five months. In September 2017, Verzenio became the first and only cyclin-dependent kinase (CDK)4 & 6 inhibitor approved in combination and as a single agent in metastatic breast cancer. Specifically, Verzenio was approved for use in combination with fulvestrant for the treatment of women with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

The recommended dose of Verzenio in combination with an AI is 150 mg orally twice daily, continued until disease progression or unacceptable toxicity. Verzenio is available in four tablet strengths (200 mg, 150 mg, 100 mg, and 50 mg).

This approval of Verzenio as initial therapy in combination with an AI is based on the efficacy and safety demonstrated in the pivotal MONARCH 3 clinical trial. MONARCH 3 is a Phase 3, randomized, double-blind, placebo-controlled trial evaluating Verzenio in combination with an AI as initial endocrine-based therapy that enrolled 493 postmenopausal women with HR+, HER2- advanced breast cancer who had no prior systemic treatment for advanced disease. In patients who received neoadjuvant/adjuvant endocrine therapy, a disease-free interval of more than 12 months since completion of endocrine therapy was required. This Verzenio new drug application was given Priority Review as part of the FDA's Expedited Programs for Serious Conditions, a program used for therapies that address an unmet medical need in the treatment of serious or life-threatening conditions, such as metastatic breast cancer. Verzenio was also granted Breakthrough Therapy Designation in 2015 based on the Phase 1 JPBA trial.

In MONARCH 3, Verzenio dosed orally at 150 mg twice daily on a continuous schedule with an AI demonstrated a greater than 28-month median progression-free survival (PFS) in patients who received initial endocrine-based therapy for metastatic disease (28.2 months [95% CI: 23.5-NR] vs 14.8 months [95% CI: 11.2-19.2] with placebo plus an AI [HR: 0.54; 95% CI: 0.418-0.698, P <0.0001]). In patients with measurable disease who received Verzenio plus an AI (n=267), an objective response rate of 55.4 percent was achieved (ORR; defined as complete response plus partial response [CR + PR], and based upon confirmed responses; PR defined as ≥30% reduction in target lesions)¹ (n=148; 95% CI: 49.5-61.4), with 52.1 percent of patients having achieved a PR (n=139) and 3.4 percent having achieved a CR (n=9).² In comparison, in the placebo-plus-AI group of patients with measurable disease (n=132), ORR was 40.2 percent (n=53; 95% CI: 31.8-48.5), with all women being partial responders. Median duration of response (DoR) was 27.4 months with Verzenio plus an AI (95% CI: 25.7-NR) versus 17.5 months with placebo plus an AI (95% CI: 11.2-22.2).

"This approval is an important milestone, as it shows that Verzenio plus an aromatase inhibitor substantially reduced tumor size and delayed disease progression in women with HR+, HER2- metastatic breast cancer. Notably, the MONARCH 3 trial included patients with certain concerning clinical characteristics, such as a pattern of disease that spread to the liver," said Joyce O'Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research and chair, Breast Cancer Research Program, Baylor University Medical Center, Texas Oncology and U.S. Oncology, Dallas, TX. "This information will help inform treatment decisions for each patient, which can be complicated in advanced breast cancer."

The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, and embryofetal toxicity. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Perform complete blood counts and liver function tests prior to the start of Verzenio treatment, every two weeks for the first two months, monthly for the next two months, and as clinically indicated. Based on results, Verzenio may require dose modification. Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. Advise patients of potential risk to a fetus and to use effective contraception. See full Prescribing Information for further management instructions. The most common adverse reactions in the MONARCH 1, 2, and 3 trials (all grades, ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

"The speed with which our team has been able to work with the FDA to gain approval for this additional Verzenio indication underscores Lilly's commitment to delivering meaningful medicines that can help more people living with advanced breast cancer," said Sue Mahony, Ph.D., senior vice president and president of Lilly Oncology. "Verzenio has now been developed, studied and clinically proven in three key trials to be effective for women with HR+, HER2- metastatic breast cancer – helping to ensure we are providing support to those who need it most."

"For those facing a diagnosis of metastatic breast cancer or learning that their disease has spread further, each new indication and clinical development is critical," said Marc Hurlbert, Ph.D., chairman, Metastatic Breast Cancer Alliance. "Today's news represents continued progress towards helping more people living with this devastating disease."

Lilly Receives Additional FDA Approval for Verzenio (abemaciclib), as Initial Treatment for Advanced Breast Cancer